Quantitative assessment of brain iron by R2* relaxometry in patients with clinically isolated syndrome and relapsing–remitting multiple sclerosis

2009 ◽  
Vol 15 (9) ◽  
pp. 1048-1054 ◽  
Author(s):  
M Khalil ◽  
C Enzinger ◽  
C Langkammer ◽  
M Tscherner ◽  
M Wallner-Blazek ◽  
...  

Background Increased iron deposition has been implicated in the pathophysiology of multiple sclerosis (MS), based on visual analysis of signal reduction on T2-weighted images. R2* relaxometry allows to assess brain iron accumulation quantitatively. Objective To investigate regional brain iron deposition in patients with a clinically isolated syndrome (CIS) or relapsing–remitting MS (RRMS) and its associations with demographical, clinical, and conventional magnetic resonance imaging (MRI) parameters. Methods We studied 69 patients (CIS, n = 32; RRMS, n = 37) with 3T MRI and analyzed regional R2* relaxation rates and their correlations with age, disease duration, disability, T2 lesion load, and normalized brain volumes. Results Basal ganglia R2* relaxation rates increased in parallel with age ( r = 0.3–0.6; P < 0.01) and were significantly higher in RRMS than in CIS ( P < 0.05). Using multivariate linear regression analysis, the rate of putaminal iron deposition was independently predicted by the patients’ age, disease duration, and gray matter atrophy. Conclusions Quantitative assessment by R2* relaxometry suggests increased iron deposition in the basal ganglia of MS patients, which is associated with disease duration and brain atrophy. This technique together with long-term follow-up thus appears suited to clarify whether regional iron accumulation contributes to MS morbidity or merely reflects an epiphenomenon.

2011 ◽  
Vol 18 (4) ◽  
pp. 433-441 ◽  
Author(s):  
R Marc Lebel ◽  
Amir Eissa ◽  
Peter Seres ◽  
Gregg Blevins ◽  
Alan H Wilman

Background: In addition to neuronal injury, inflammatory, and demyelinating processes, evidence suggests multiple sclerosis (MS) is also associated with increased iron deposition in the basal ganglia. Magnetic resonance imaging (MRI), particularly at very high field strengths, is sensitive to iron accumulation and may enable visualization and quantification of iron associated with MS. Objectives: To investigate the sub-cortical gray matter in patients with early-stage relapsing–remitting MS using multiple, and novel, quantitative MRI measures at very high field. Methods: In total, 22 patients with relapsing–remitting MS and 22 control subjects were imaged at 4.7 Tesla. Transverse relaxation rates (R2 and R2*) and susceptibility phase were quantified in four basal ganglia nuclei, the thalamus, and the red nuclei. Parameters in patients with MS were compared with those in healthy subjects and correlated with clinical scores. Results: Significant abnormalities were observed in most structures, most notably in the pulvinar sub-nucleus. Significant correlations with disability were observed in the pulvinar; marginally significant correlations were also observed in the thalamus and red nucleus. No significant correlations were observed with duration since index relapse. Conclusions: Widespread abnormalities are present in the deep gray matter nuclei of patients recently diagnosed with MS; these abnormalities can be detected via multi-modal high-field MRI. Imaging metrics, particularly R2*, relate to disease severity in the pulvinar and other gray matter regions.


2010 ◽  
Vol 63 (3) ◽  
pp. 136-143 ◽  
Author(s):  
A. Burgetova ◽  
Z. Seidl ◽  
J. Krasensky ◽  
D. Horakova ◽  
M. Vaneckova

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Maria Eleftheria Evangelopoulos ◽  
Georgios Koutsis ◽  
Manolis Markianos

Several studies have investigated leptin levels in patients with multiple sclerosis (MS) with somewhat conflicting results. They have all focused on patients with established relapsing-remitting (RR) MS but have not specifically looked at patients with clinically isolated syndrome (CIS) suggestive of MS, in the early stages of disease. In this study, serum leptin levels were measured in 89 treatment-naïve patients with CIS (53 patients) or RRMS (36 patients) and 73 controls searching for differences between the groups and for associations with several disease parameters. The expected significant sexual dimorphism in leptin levels (higher levels in females) was observed in both MS patients and controls. Increased leptin levels were found in female patients with RRMS compared to female controls (P=.003) and female CIS patients (P=.001). Female CIS patients had comparable levels to controls. Leptin levels correlated positively to disease duration, but not to EDSS, in female patients with RRMS. The results of the present study do not indicate involvement of leptin in the early stages of MS. Normal leptin levels in patients with CIS suggest that leptin does not have a pathogenic role. The ratio leptin/BMI increases during disease course in female MS patients in a time-dependent and disability-independent manner.


2016 ◽  
Vol 22 (12) ◽  
pp. 1560-1568 ◽  
Author(s):  
M Khalil ◽  
A Renner ◽  
C Langkammer ◽  
C Enzinger ◽  
S Ropele ◽  
...  

Background: Lipocalin 2 (LCN2) may be involved in the immunopathogenesis of multiple sclerosis (MS) and might further impact on iron homoeostasis. Brain iron accumulates in MS; however, the association to iron-related proteins is still unsolved. Objective: To investigate cerebrospinal fluid (CSF) and serum LCN2, transferrin (Trf) and ferritin in early MS in relation to disease evolution and longitudinal brain iron accumulation. Methods: We analysed CSF and serum LCN2 by enzyme-linked immunosorbent assay (ELISA) and Trf and ferritin by nephelometry in 55 patients (45 clinically isolated syndrome (CIS), 10 MS, median clinical follow-up 4.8 years) and 63 controls. In patients, we assessed sub-cortical grey matter iron by 3T magnetic resonance imaging (MRI) R2* relaxometry (median imaging follow-up 2.2 years). Results: Compared to controls serum ( p < 0.01), CSF ( p < 0.001) LCN2 and CSF Trf ( p < 0.001) levels were reduced in the patients. CSF LCN2 correlated with CSF Trf ( r = 0.5, p < 0.001). In clinically stable patients, CSF LCN2 levels correlated with basal ganglia iron accumulation ( r = 0.5, p < 0.05). In CIS, higher CSF LCN2 levels were associated with conversion to clinically definite MS ( p < 0.05). Conclusion: We demonstrate altered LCN2 regulation in early MS and provide first evidence for this to be possibly linked to both clinical MS activity and iron accumulation in the basal ganglia.


2013 ◽  
Vol 71 (5) ◽  
pp. 275-279 ◽  
Author(s):  
Denis Bernardi Bichuetti ◽  
Enedina Maria Lobato de Oliveira ◽  
Nilton Amorin de Souza ◽  
Mar Tintoré ◽  
Alberto Alain Gabbai

Although neuromyelitis optica (NMO) is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS), few studies comparing both conditions in a single center have been done.Methods:Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007.Results:Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062) with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013) and progression index (0.9 versus 0.6, p≪0.0001), with more patients reaching expanded disability status scale (EDSS) 6.0 (39 versus 17%, p=0.0036). The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15.Conclusion:Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.


2021 ◽  
Vol 11 (11) ◽  
pp. 1444
Author(s):  
Mattia Fonderico ◽  
Emilio Portaccio ◽  
Lorenzo Razzolini ◽  
Luisa Pastò ◽  
Angelo Bellinvia ◽  
...  

The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.


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